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Cassandra Clift, PhD




Research Fellow




Research Fellow




Cassandra L. Clift, Mark C. Blaser, Willem Gerrits, Tan Pham, Mandy E. Turner, Jason L. Andresen, Owen S. Fenton, Joshua M. Grolman, Fabrizio Buffolo, David J. Mooney, Jesper Hjortnaes, Jochen D. Muehlschlegel, Masanori Aikawa, Sasha A. Singh, Robert Langer, Elena Aikawa

Multi-Omics Driven Assessment of Pathobiology in a 3D-Bioprinted Aortic Valve Disease Model Compared to Native Valves and 2D Culture

I received my bachelor’s degree in Biomedical Engineering and my PhD in mass spectrometry driven studies of extracellular matrix dysregulation in congenital aortic valve disease. My primary research goals are to use novel multi-omics techniques mixed with biomaterial applications to design better bioengineered cardiovascular disease models and to identify novel pharmacotherapeutic targets. I believe symposiums such as the WMSS are critical to our community. The WMSS symposium allows women in science like myself to continuously advocate for ourselves and our community, display our scientific knowledge, celebrate our accomplishments, and build strong collaborations with other female scientists.

Background: During calcific aortic valve disease (CAVD) progression, mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, which further disrupts cellular-driven pathophysiology and valve biomechanics. Currently, no pharmacotherapeutics are available for CAVD, due in part to the lack of 1) appropriate experimental models that recapitulate this complex biomechanical environment; and 2) studies that adequately assess the complexity of novel engineered valvular model systems.

Methods: Three models of CAVD were used in this study: 1) traditional 2D- valve interstitial cell (VIC) monoculture; 2) VICs encapsulated in 3D-bioprinted models; and 3) human CAVD valve leaflets. Multi-omics LC-MS/MS analysis were performed to probe the cellular proteome, extracellular matrisome, vesiculome, and n-glycome.

Results: Cellular proteomics identified over 2500 proteins. The 2D-cellular proteome was enriched in biological processes of actin organization and platelet aggregation, while the 3D-bioprinted cellular proteome was enriched in glycosaminoglycan biosynthesis, and extracellular-matrix organization. 3D-printed cellular proteomics also identified enzymatic regulators of glycosylation, informing downstream N-glycome composition. Extracellular vesiculomics identified over 200 proteins, including 14 vesicle markers. Additionally, extracellular-matrisomics probed site-specificity and abundance of several post-translational modfications of collagen subtypes.

Conclusion: This study positions multi-omics as a novel technique for the design and assessment of bioengineered model systems.